Progressive multifocal leukoencephalopathy during fumarate monotherapy of psoriasis.

Abstract

In September 2013, a 69-year-old Caucasian man who was anti–JC virus (JCV) antibody positive was admitted to our hospital with slowly progressing right hemiparesis and aphasia lasting for approximately 6 months. Medical history revealed arterial hypertension, biological aortic valve replacement, and psoriasis vulgaris, treated with 3–6 tablets daily of dimethylfumarate (DMF; 120 mg)/ethylhydrogenfumarate (EHF; 95 mg) (Fumaderm, Biogen Idec, Ismaning, Germany) since December 2008 (table e-1 at [Neurology.org/nn][1]). No other immunosuppressive pretreatment had been given. In April/May 2013, the patient recognized a steadily progressing weakness of the right leg. In June 2013, an external diagnosis of ischemic stroke was made. An MRI scan (figure e-1), which was performed after deterioration of clinical symptoms, revealed a subcortical left hemispheric lesion; biopsy demonstrated macrophage-dominated inflammation, dysmorphic astrocytes, simian virus 40 positivity, and several p53- and MiB1-positive cells, suggestive of a JCV encephalitis (figure e-2). JCV DNA was detected in CSF at 2 different time points using a highly sensitive PCR protocol (September 24, 2013, 16 copies/mL; October 7, 2013, 42 copies/mL),1 leading to the diagnosis of progressive multifocal leukoencephalopathy (PML) in September 2013. Further diagnostic workup (table e-2) unmasked toxic bone marrow damage (figure e-3) and an increased excretion of kappa light chains in urine without any evidence for a plasmocytoma. Taking into account the patient's initial presentation with a slowly progressive paresis since April/May 2013 as well as the initial MRI scan (figure e-1), which is compatible with the PML diagnosis, we believe that the onset of PML was in April/May without preexisting leukopenia and only moderate lymphopenia (grade 2 lymphopenia: 724–738 cells/µL, figure). Several weeks later, white blood cell count dropped to a minimum of 4,800 cells/µL with 288 cells/µL lymphocytes under continuous Fumaderm treatment. Fumaderm was discontinued, and treatment with mirtazapine (45 mg/day; Remergil, MSD Sharp und Dohme GmbH, Haar, Germany), mefloquine (250 mg/week; Lariam, Roche Pharma AG, Grenzach-Wyhlen, Germany), and levetiracetam (1,000 mg/day; Keppra, UCB Pharma GmbH, Monheim, Germany) was initiated.2 Acknowledgment: The authors thank Prof. Dr. med. Anke Reinacher-Schick for her great support in hemato-oncologic diagnostics and Prof. Dr. med. Andrea Tannapfel/Dr. med. M. Gruener for providing pictures of the bone marrow biopsy. [1]: http://Neurology.org/nn